Hindbrain estrogen receptor regulation of ventromedial hypothalamic glycogen metabolism and glucoregulatory transmitter expression in the hypoglycemic male rat.
Animals
Brain-Derived Neurotrophic Factor
/ metabolism
Corticosterone
/ metabolism
Glucose
/ metabolism
Glycogen
/ metabolism
Hypoglycemia
/ metabolism
Male
Nitric Oxide
/ metabolism
Norepinephrine
/ metabolism
Piperidines
/ pharmacology
Pyrazoles
/ pharmacology
Pyrimidines
/ pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Estrogen
/ antagonists & inhibitors
Rhombencephalon
/ drug effects
Ventromedial Hypothalamic Nucleus
/ drug effects
MPP
PHTPP
glutamate decarboxylase
glycogen
nitric oxide synthase
norepinephrine
Journal
Neuroscience
ISSN: 1873-7544
Titre abrégé: Neuroscience
Pays: United States
ID NLM: 7605074
Informations de publication
Date de publication:
15 06 2019
15 06 2019
Historique:
received:
16
10
2018
revised:
25
03
2019
accepted:
26
03
2019
pubmed:
8
4
2019
medline:
10
1
2020
entrez:
8
4
2019
Statut:
ppublish
Résumé
Estrogen receptor-alpha (ERα) and -beta (ERβ) occur in key elements of the brain gluco-homeostatic network in both sexes, including the hindbrain dorsal vagal complex (DVC), but the influence of distinct receptor populations on this critical function is unclear. The ventromedial hypothalamic nucleus (VMN) maintains glucose balance by integrating nutrient, endocrine, and neurochemical cues, including metabolic sensory information supplied by DVC A2 noradrenergic neurons. Current research utilized the selective ERα and ERβ antagonists MPP and PHTPP to characterize effects of DVC ERs on VMN norepinephrine (NE) activity and metabolic neurotransmitter signaling in insulin-induced hypoglycemic (IIH) male rats. Data show that ERβ inhibits VMN glycogen synthase and stimulates phosphorylase protein expression, while attenuating hypoglycemic augmentation of glycogen content. Furthermore, both ERs attenuate VMN glucose concentrations during IIH. Hypoglycemic up-regulation of nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) signaling was correspondingly driven by ERα or -β, whereas GABA and steroidogenic factor-1 were respectively suppressed independently of ER input or by ERβ. IIH intensified VMN NE accumulation by ERβ-dependent mechanisms, but did not alter NE levels in other gluco-regulatory loci. ERβ amplified the magnitude of insulin-induced decline in blood glucose. Both ERs regulate corticosterone, but not glucagon secretion during IIH and oppose hypoglycemic diminution of circulating free fatty acids. These findings identify distinguishing versus common VMN functions targeted by DVC ERα and -β. Sex differences in hypoglycemic VMN NE accumulation, glycogen metabolism, and transmitter signaling may involve, in part, discrepant regulatory involvement or differential magnitude of impact of these hindbrain ERs.
Identifiants
pubmed: 30954669
pii: S0306-4522(19)30215-5
doi: 10.1016/j.neuroscience.2019.03.053
pmc: PMC6594372
mid: NIHMS1034096
pii:
doi:
Substances chimiques
1,3-bis(4-hydroxyphenyl)-4-methyl-5-(4-(2-piperidinylethoxy)phenol)-1H-pyrazole
0
4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo(1,5-a)pyrimidin-3-yl)phenol
0
Brain-Derived Neurotrophic Factor
0
Piperidines
0
Pyrazoles
0
Pyrimidines
0
Receptors, Estrogen
0
Nitric Oxide
31C4KY9ESH
Glycogen
9005-79-2
Glucose
IY9XDZ35W2
Corticosterone
W980KJ009P
Norepinephrine
X4W3ENH1CV
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
253-260Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK109382
Pays : United States
Informations de copyright
Copyright © 2019. Published by Elsevier Ltd.
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